Do you have a program such as CCleaner clearing up files? If yes, then you need to set up exclusion of any thunderbird files and folders.

I have run CCleaner frequently for years without it causing this problem, including having it compact the Thunderbird database, but to be safe, I'm taking your advice and see what happens. I recently noticed that when I attempted to change the name of several saved searches in TB version 52.1.1, it reset the search settings, though that is not the only situation that has caused this.

This is getting ridiculous. Thunderbird KEEPS destroying all my search folder settings. I suspect it could be connected to updates among other things. After the last update 52.2.1, I immediately checked my search folders and all was well, but a few days later, boom! All my search folders settings were gone. In this case CCleaner was not the culprit. Something is wrong with Thunderbird. Related: Where are the search folder settings stored? If I know the folder/file then I can reload them from a backup.

I found the location of the search folders for Windows 10: Users\<username>\AppData\Roaming\Thunderbird\Profiles\<activeprofile>\virtualFolders.dat

I restored from yesterday's backup to get my search folder settings back.

This doesn't solve the problem. The latest versions of Thunderbird seems to have an instability. I've also noticed that in recent days some emails show up with blank Subjects and refuse to delete, or that the Junk icon won't be active for some emails. Very odd behavior.

Newest versions (2017) of Thunderbird need to be avoided like the plague. They keep erasing search folder criteria.

My Saved Searches remain intact, using current and beta versions of Thunderbird.

I do not use CCleaner. Are you still using CCleaner? If you must, please exclude the Thunderbird profile from its machinations.

I excluded Thunderbird from CCleaner when Toad-Hall brought it up. In addition, there were two times that TB reset all my search folders when I know I had not run CCleaner.

I have conclusively shown to myself that CCleaner is not the cause of TB resetting the search folders. I'm now suspecting Smart Defrag causing some hiccup in TB.

This is still happening. Frequently as in once or more per week. I copy the virtualfolders.dat file from backup and that usually fixes it, though I may have to go back several backups before I find one that works.